Dataset Information

Role of Mir-155 in Controlling HIF-1? Level and Promoting Endothelial Cell Maturation.

ABSTRACT: Stem-cell-based therapy for cardiovascular disease, especially ischemic heart disease (IHD), is a promising approach to facilitating neovascularization through the migration of stem cells to the ischemic site and their subsequent differentiation into endothelial cells (ECs). Hypoxia is a chief feature of IHD and the stem cell niche. However, whether hypoxia promotes stem cell differentiation into ECs or causes them to retain their stemness is controversial. Here, the differentiation of pluripotent stem cells (iPSCs) into endothelial cells (ECs) was induced under hypoxia. Though the angiogenic capability and angiogenesis-related autocrine/paracrine factors of the ECs were improved under hypoxia, the level of hypoxia inducible factor 1? (HIF-1?) was nonetheless found to be restricted along with the EC differentiation. The down-regulation of HIF-1? was found to have been caused by VEGF-induced microRNA-155 (miR-155). Moreover, miR-155 was also found to enhance the angiogenic capability of induced ECs by targeting E2F2 transcription factor. Hence, miR-155 not only contributes to controlling HIF-1? expression under hypoxia but also promotes angiogenesis, which is a key feature of mature ECs. Revealing the real role of hypoxia and clarifying the function of miR-155 in EC differentiation may facilitate improvement of angiogenic gene- and stem-cell-based therapies for ischemic heart disease.

SUBMITTER: Yang D

PROVIDER: S-EPMC5059686 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Role of Mir-155 in Controlling HIF-1α Level and Promoting Endothelial Cell Maturation.

Yang Deguang D Wang Jinhong J Xiao Meng M Zhou Tao T Shi Xu X

Scientific reports 20161012

Stem-cell-based therapy for cardiovascular disease, especially ischemic heart disease (IHD), is a promising approach to facilitating neovascularization through the migration of stem cells to the ischemic site and their subsequent differentiation into endothelial cells (ECs). Hypoxia is a chief feature of IHD and the stem cell niche. However, whether hypoxia promotes stem cell differentiation into ECs or causes them to retain their stemness is controversial. Here, the differentiation of pluripote ...[more]

PMID: 27731397

Similar Datasets

Project description:BackgroundAccumulating evidence indicates that dysregulation of miR-182-5p can serve as diagnostic and prognostic biomarkers for some cancers, whereas the role of miR-182-5p has not been explored in nasopharyngeal carcinoma (NPC). Our study aims to elucidate the biological function of miR-182-5p in NPC and the potential molecular mechanism involved.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine miR-182-5p expression in NPC primary tissues and cell lines. Immunohistochemistry (IHC) for ZFP36L1 was conducted in NPC samples. Western blot was used to evaluate protein expression in cell lines. A series of functional assays were carried out to evaluate the roles of miR-182-5p and ZFP36L1 in tumor development and progression of NPC. Bioinformatics tools and luciferase reporter assays were utilized to identify the potential mechanisms of action. Moreover, rescue experiments were applied to explore whether ZFP36L1 mediated the effects of miR-182-5p in NPC.ResultsUp-regulation of miR-182-5p was significantly associated with tumor development and poor prognosis in patients with NPC. Functional study demonstrated that miR-182-5p overexpression enhanced, whereas suppression of miR-182-5p impeded NPC cell proliferation, migration, tumorigenesis and metastasis. Mechanistically, miR-182-5p interacted with ZFP36L1 at two sites in its 3' un-translated region (UTR) and repressed ZFP36L1 expression in NPC. Consistently, an inverse correlation was observed between the expression levels of miR-182-5p and ZFP36L1 using clinical NPC tissues, and down-regulation of ZFP36L1 in NPC predicts poor survival. Furthermore, overexpression of miR-182-5p in NPC was partly attributable to the transcriptional activation effect induced by hypoxia-inducible factor 1α (HIF-1α).ConclusionsOur data suggests that miR-182-5p facilitates cell proliferation and migration in NPC through its ability to down-regulate ZFP36L1 expression, and that the HIF-1α/miR-182-5p/ZFP36L1 axis may serve as a novel therapeutic target in the management of NPC.

Dataset Information

Role of Mir-155 in Controlling HIF-1? Level and Promoting Endothelial Cell Maturation.

Publications

Role of Mir-155 in Controlling HIF-1α Level and Promoting Endothelial Cell Maturation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets